Acta Diabetologica

, Volume 51, Issue 6, pp 905–915 | Cite as

Updating the natural history of diabetic nephropathy

  • Giuseppe PuglieseEmail author
Review Article


Diabetic nephropathy (DN) is a major cause of morbidity and mortality in patients with both types of diabetes and the leading cause of end-stage renal disease (ESRD) worldwide. The classical, five-stage natural history of DN, after an initial phase of hyperfiltration, is characterized by a progressive increase of albuminuria from normoalbuminuria to proteinuria, followed by a decline of glomerular filtration rate (GFR). Accumulating evidence indicates that clinical course of DN has changed profoundly, likely as a consequence of changes in treatment. In fact, remission/regression of microalbuminuria is a common feature of both type 1 and 2 diabetes which far outweighs progression to proteinuria. Moreover, GFR loss has been shown to occur independently of albuminuria or even in the absence of it. Nonalbuminuric renal impairment probably represents a different pathway to loss of renal function, which might recognize different pathogenic mechanisms, prognostic implications, and possibly therapeutic measures, as compared with the albuminuric pathway. The nonalbuminuric phenotype might be related to macroangiopathy instead of microangiopathy and/or be the consequence of repeated and/or unresolved episodes of acute kidney injury, even of mild degree. Reduced GFR and albuminuria are both powerful risk factor for cardiovascular events, whereas albuminuria appears to predict death and progression to ESRD better than GFR loss. Finally, it is unclear whether reduced GFR and albuminuria warrant different interventions and whether GFR decline may also regress in response to treatment, as proteinuria does. Further epidemiological, pathologic, pathophysiological, and intervention studies are needed to clarify the distinctive features of nonalbuminuric renal impairment.


Chronic kidney disease Albuminuria GFR decline Cardiovascular disease 



Diabetic nephropathy


End-stage renal disease


Cardiovascular disease


Glomerular filtration rate


Blood pressure


Albumin excretion rate


Renin–angiotensin system


Estimated GFR


Hemoglobin A1c


Tumor necrosis factor receptor


Chronic kidney disease


National Health and Nutrition Examination Survey


Developing Education on Microalbuminuria for Awareness of renal and cardiovascular risk in Diabetes


United Kingdom Prospective Diabetes Study


Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications


National Evaluation of the Frequency of Renal Impairment cO-existing with NIDDM


Renal Insufficiency And Cardiovascular Events


Prevalence of chronic kidney disease in patients with type 2 diabetes in Spain


Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation


Fenofibrate Intervention and Event Lowering in Diabetes


Modification of Diet in Renal Disease


CKD-Epidemiology Collaboration


Atherosclerosis Risk in Communities


Acute kidney injury


Kidney Disease Improving Global Outcomes


Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan



The content of this article was the subject of the 12th Ruth Osterby Lecture, given by Professor Pugliese at the 27th Annual General Meeting of the European Diabetic Nephropathy Study Group (EDNSG), which was held in London, UK, on May 16–17, 2014. The Author thanks the RIACE Investigators for participating in the studies cited in this article. The RIACE study cited in this article was supported by the Research Foundation of the Italian Society of Diabetology (Fo.Ri.SID) and the Diabetes, Endocrinology and Metabolism (DEM) Foundation, and by unconditional grants from Eli-Lilly, Takeda, Chiesi Farmaceutici and Boehringer-Ingelheim.

Conflict of interest


Human and animal rights

This article does not contain any studies with human or animal subjects performed by any of the authors.


  1. 1.
    Reutens AT, Atkins RC (2011) Epidemiology of diabetic nephropathy. Contrib Nephrol 170:1–7PubMedCrossRefGoogle Scholar
  2. 2.
    Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053PubMedCrossRefGoogle Scholar
  3. 3.
    Ritz E, Rychlík I, Locatelli F, Halimi S (1999) End-stage renal failure in type 2 diabetes: a medical catastrophe of worldwide dimensions. Am J Kidney Dis 34:795–808PubMedCrossRefGoogle Scholar
  4. 4.
    Gregg EW, Li Y, Wang J, Burrows NR, Ali MK, Rolka D, Williams DE, Geiss L (2014) Changes in diabetes-related complications in the United States, 1990–2010. N Engl J Med 370:1514–1523PubMedCrossRefGoogle Scholar
  5. 5.
    Mogensen CE (1999) Microalbuminuria, blood pressure and diabetic renal disease: origin and development of ideas. Diabetologia 42:263–285PubMedCrossRefGoogle Scholar
  6. 6.
    Jerums G, Premaratne E, Panagiotopoulos S, MacIsaac RJ (2010) The clinical significance of hyperfiltration in diabetes. Diabetologia 53:2093–2104PubMedCrossRefGoogle Scholar
  7. 7.
    Viberti GC, Hill RD, Jarrett RJ, Argyropoulos A, Mahmud U, Keen H (1982) Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1:1430–1432PubMedCrossRefGoogle Scholar
  8. 8.
    Parving HH, Oxenbøll B, Svendsen PA, Christiansen JS, Andersen AR (1982) Early detection of patients at risk of developing diabetic nephropathy: a longitudinal study of urinary albumin excretion. Acta Endocrinol (Copenh) 100:550–555Google Scholar
  9. 9.
    Mogensen CE, Christensen CK (1984) Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311:89–93PubMedCrossRefGoogle Scholar
  10. 10.
    Mathiesen ER, Oxenbøll B, Johansen K, Svendsen PA, Deckert T (1984) Incipient nephropathy in type 1 (insulin-dependent) diabetes. Diabetologia 26:406–410PubMedCrossRefGoogle Scholar
  11. 11.
    Mogensen CE (1984) Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 310:356–360PubMedCrossRefGoogle Scholar
  12. 12.
    Tanaka Y, Atsumi Y, Matsuoka K, Onuma T, Tohjima T, Kawamori R (1998) Role of glycemic control and blood pressure in the development and progression of nephropathy in elderly Japanese NIDDM patients. Diabetes Care 21:116–120PubMedCrossRefGoogle Scholar
  13. 13.
    Ravid M, Savin H, Jutrin I, Bental T, Katz B, Lishner M (1993) Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med 118:577–581PubMedCrossRefGoogle Scholar
  14. 14.
    Ahmad J, Siddiqui MA, Ahmad H (1997) Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria. Diabetes Care 20:1576–1581PubMedCrossRefGoogle Scholar
  15. 15.
    Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS (2003) Regression of microalbuminuria in type 1 diabetes. N Engl J Med 348:2285–2293PubMedCrossRefGoogle Scholar
  16. 16.
    Giorgino F, Laviola L, Cavallo Perin P, Solnica B, Fuller J, Chaturvedi N (2004) Factors associated with progression to macroalbuminuria in microalbuminuric type 1 diabetic patients: the EURODIAB Prospective Complications Study. Diabetologia 47:1020–1028PubMedCrossRefGoogle Scholar
  17. 17.
    Hovind P, Tarnow L, Rossing P, Jensen BR, Graae M, Torp I, Binder C, Parving HH (2004) Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study. BMJ 328:1105PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Gaede P, Tarnow L, Vedel P, Parving HH, Pedersen O (2004) Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria. Nephrol Dial Transplant 19:2784–2788PubMedCrossRefGoogle Scholar
  19. 19.
    Araki S, Haneda M, Sugimoto T, Isono M, Isshiki K, Kashiwagi A, Koya D (2005) Factors associated with frequent remission of microalbuminuria in patients with type 2 diabetes mellitus. Diabetes 54:2983–2987PubMedCrossRefGoogle Scholar
  20. 20.
    Yamada T, Komatsu M, Komiya I, Miyahara Y, Shima Y, Matsuzaki M, Ishikawa Y, Mita R, Fujiwara M, Furusato N, Nishi K, Aizawa T (2005) Development, progression, and regression of microalbuminuria in Japanese patients with type 2 diabetes under tight glycemic and blood pressure control: the Kashiwa study. Diabetes Care 28:2733–2738PubMedCrossRefGoogle Scholar
  21. 21.
    Tabaei BP, Al-Kassab AS, Ilag LL, Zawacki CM, Herman WH (2001) Does microalbuminuria predict diabetic nephropathy? Diabetes Care 24:1560–1566PubMedCrossRefGoogle Scholar
  22. 22.
    Perkins BA, Krolewski AS (2009) Early nephropathy in type 1 diabetes: the importance of early renal function decline. Curr Opin Nephrol Hypertens 18:233–240PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Perkins BA, Ficociello LH, Ostrander BE, Silva KH, Weinberg J, Warram JH, Krolewski AS (2007) Microalbuminuria and the risk for early progressive renal function decline in type 1 diabetes. J Am Soc Nephrol 18:1353–1361PubMedCrossRefGoogle Scholar
  24. 24.
    Krolewski AS, Niewczas MA, Skupien J, Gohda T, Smiles A, Eckfeldt JH, Doria A, Warram JH (2014) Early progressive renal decline precedes the onset of microalbuminuria and its progression to macroalbuminuria. Diabetes Care 37:226–234PubMedCrossRefGoogle Scholar
  25. 25.
    Skupien J, Warram JH, Smiles AM, Niewczas MA, Gohda T, Pezzolesi MG, Cantarovich D, Stanton R, Krolewski AS (2012) The early decline in renal function in patients with type 1 diabetes and proteinuria predicts the risk of end-stage renal disease. Kidney Int 82:589–597PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Skupien J, Warram JH, Smiles A, Galecki A, Stanton RC, Krolewski AS (2014) Improved glycemic control and risk of ESRD in patients with type 1 diabetes and proteinuria. J Am Soc Nephrol. doi: 10.1681/ASN.2013091002
  27. 27.
    Skupien J, Warram JH, Niewczas MA, Gohda T, Malecki M, Mychaleckyj JC, Galecki AT, Krolewski AS (2014) Synergism between circulating tumor necrosis factor receptor 2 and HbA1c in determining renal decline during 5-18 years of follow-up in patients with type 1 diabetes and proteinuria. Diabetes Care 37:2601–2608PubMedCrossRefGoogle Scholar
  28. 28.
    Sabbisetti VS, Waikar SS, Antoine DJ, Smiles A, Wang C, Ravisankar A, Ito K, Sharma S, Ramadesikan S, Lee M, Briskin R, De Jager PL, Ngo TT, Radlinski M, Dear JW, Park KB, Betensky R, Krolewski AS, Bonventre JV (2014) Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. J Am Soc Nephrol. doi: 10.1681/ASN.2013070758
  29. 29.
    Lacquaniti A, Donato V, Pintaudi B, Di Vieste G, Chirico V, Buemi A, Di Benedetto A, Arena A, Buemi M (2013) “Normoalbuminuric” diabetic nephropathy: tubular damage and NGAL. Acta Diabetol 50:935–942PubMedCrossRefGoogle Scholar
  30. 30.
    Kopf S, Oikonomou D, von Eynatten M, Kieser M, Zdunek D, Hess G, Morcos M, Forsblom C, Bierhaus A, Groop PH, Nawroth PP, Humpert PM (2014) Urinary excretion of high molecular weight adiponectin is an independent predictor of decline of renal function in type 2 diabetes. Acta Diabetol 51:479–489PubMedGoogle Scholar
  31. 31.
    Lane PH, Steffes MW, Mauer SM (1992) Glomerular structure in IDDM women with low glomerular filtration rate and normal urinary albumin excretion. Diabetes 41:581–586PubMedCrossRefGoogle Scholar
  32. 32.
    Tsalamandris C, Allen TJ, Gilbert RE, Sinha A, Panagiotopoulos S, Cooper ME, Jerums G (1994) Progressive decline in renal function in diabetic patients with and without albuminuria. Diabetes 43:649–655PubMedCrossRefGoogle Scholar
  33. 33.
    Kramer HJ, Nguyen QD, Curhan G, Hsu CY (2003) Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus. JAMA 289:3273–3277PubMedCrossRefGoogle Scholar
  34. 34.
    MacIsaac RJ, Tsalamandris C, Panagiotopoulos S, Smith TJ, McNeil KJ, Jerums G (2004) Nonalbuminuric renal insufficiency in type 2 diabetes. Diabetes Care 27:195–200PubMedCrossRefGoogle Scholar
  35. 35.
    Dwyer JP, Parving HH, Hunsicker LG, Ravid M, Remuzzi G, Lewis JB, DEMAND Investigators (2012) Renal dysfunction in the presence of normoalbuminuria in type 2 diabetes: results from the DEMAND study. Cardiorenal Med 2:1–10PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR; UKPDS Study Group (2006) Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes 55:1832–1839CrossRefGoogle Scholar
  37. 37.
    Molitch ME, Steffes M, Sun W, Rutledge B, Cleary P, de Boer IH, Zinman B, Lachin J, Epidemiology of Diabetes Interventions and Complications Study Group (2010) Development and progression of renal insufficiency with and without albuminuria in adults with type 1 diabetes in the diabetes control and complications trial and the epidemiology of diabetes interventions and complications study. Diabetes Care 33:1536–1543PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Thomas MC, Macisaac RJ, Jerums G, Weekes A, Moran J, Shaw JE, Atkins RC (2009) Nonalbuminuric renal impairment in type 2 diabetic patients and in the general population (national evaluation of the frequency of renal impairment cO-existing with NIDDM [NEFRON] 11). Diabetes Care 32:1497–1502PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, Trevisan R, Vedovato M, Gruden G, Cavalot F, Cignarelli M, Laviola L, Morano S, Nicolucci A, Pugliese G, Renal Insufficiency And Cardiovascular Events (RIACE) Study Group (2011) Clinical significance of nonalbuminuric renal impairment in type 2 diabetes. J Hypertens 29:1802–1809PubMedCrossRefGoogle Scholar
  40. 40.
    Rodriguez-Poncelas A, Garre-Olmo J, Franch-Nadal J, Diez-Espino J, Mundet-Tuduri X, Barrot-De la Puente J, Coll-de Tuero G (2013) RedGDPS Study Group Prevalence of chronic kidney disease in patients with type 2 diabetes in Spain: PERCEDIME2 study. BMC Nephrol 14:46PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Mottl AK, Kwon KS, Mauer M, Mayer-Davis EJ, Hogan SL, Kshirsagar AV (2013) Normoalbuminuric diabetic kidney disease in the U.S. population. J Diabetes Complications 27:123–127PubMedCrossRefGoogle Scholar
  42. 42.
    Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, Patel A, Cass A, Neal B, Poulter N, Mogensen CE, Cooper M, Marre M, Williams B, Hamet P, Mancia G, Woodward M, Macmahon S, Chalmers J, ADVANCE Collaborative Group (2009) Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol 20:1813–1821PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Drury PL, Ting R, Zannino D, Ehnholm C, Flack J, Whiting M, Fassett R, Ansquer JC, Dixon P, Davis TM, Pardy C, Colman P, Keech A (2011) Estimated glomerular filtration rate and albuminuria are independent predictors of cardiovascular events and death in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetologia 54:32–43PubMedCrossRefGoogle Scholar
  44. 44.
    Rigalleau V, Lasseur C, Raffaitin C, Beauvieux MC, Barthe N, Chauveau P, Combe C, Gin H (2007) Normoalbuminuric renal-insufficient diabetic patients: a lower-risk group. Diabetes Care 30:2034–2039PubMedCrossRefGoogle Scholar
  45. 45.
    Pugliese G, Solini A, Bonora E, Orsi E, Zerbini G, Giorgino F, Cavalot F, Pontiroli AE, Baroni MG, Morano S, Nicolucci A, Penno G (2011) The Chronic Kidney Disease Epidemiology Collaboration (CKD–EPI) equation provides a better definition of cardiovascular burden associated with CKD than the Modification of Diet in Renal Disease (MDRD) Study formula in subjects with type 2 diabetes. Atherosclerosis 218:194–199PubMedCrossRefGoogle Scholar
  46. 46.
    Pugliese G, Solini A, Fondelli C, Trevisan R, Vedovato M, Nicolucci A, Penno G, Renal Insufficiency And Cardiovascular Events (RIACE) Study Group (2011) Reproducibility of albuminuria in type 2 diabetic subjects. Findings from the Renal Insufficiency And Cardiovascular Events (RIACE) study. Nephrol Dial Transplant 26:3950–3954PubMedCrossRefGoogle Scholar
  47. 47.
    de Boer IH, Steffes MW (2007) Glomerular filtration rate and albuminuria: twin manifestations of nephropathy in diabetes. J Am Soc Nephrol 18:1036–1037PubMedCrossRefGoogle Scholar
  48. 48.
    Caramori ML, Fioretto P, Mauer M (2000) The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes 49:1399–1408PubMedCrossRefGoogle Scholar
  49. 49.
    Yokoyama H, Sone H, Oishi M, Kawai K, Fukumoto Y, Kobayashi M, Japan Diabetes Clinical Data Management Study Group (2009) Prevalence of albuminuria and renal insufficiency and associated clinical factors in type 2 diabetes: the Japan Diabetes Clinical Data Management study (JDDM15). Nephrol Dial Transplant 24:1212–1219PubMedCrossRefGoogle Scholar
  50. 50.
    Afghahi H, Cederholm J, Eliasson B, Zethelius B, Gudbjörnsdottir S, Hadimeri H, Svensson MK (2011) Risk factors for the development of albuminuria and renal impairment in type 2 diabetes–the Swedish National Diabetes Register (NDR). Nephrol Dial Transplant 26:1236–1243PubMedCrossRefGoogle Scholar
  51. 51.
    Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, Morano S, Cavalot F, Lamacchia O, Laviola L, Nicolucci A, Pugliese G, Renal Insufficiency And Cardiovascular Events Study Group (2013) HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study. Diabetes Care 36:2301–2310PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Penno G, Solini A, Zoppini G, Orsi E, Zerbini G, Trevisan R, Gruden G, Cavalot F, Laviola L, Morano S, Nicolucci A, Pugliese G, Renal Insufficiency And Cardiovascular Events (RIACE) Study Group (2012) Rate and determinants of association between advanced retinopathy and chronic kidney disease in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study. Diabetes Care 35:2317–2323PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Bash LD, Selvin E, Steffes M, Coresh J, Astor BC (2008) Poor glycemic control in diabetes and the risk of incident chronic kidney disease even in the absence of albuminuria and retinopathy: atherosclerosis Risk in Communities (ARIC) Study. Arch Intern Med 168:2440–2447PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Kramer CK, Leitão CB, Pinto LC, Silveiro SP, Gross JL, Canani LH (2007) Clinical and laboratory profile of patients with type 2 diabetes with low glomerular filtration rate and normoalbuminuria. Diabetes Care 30:1998–2000PubMedCrossRefGoogle Scholar
  55. 55.
    Caramori ML, Fioretto P, Mauer M (2003) Low glomerular filtration rate in normoalbuminuric type 1 diabetic patients: an indicator of more advanced glomerular lesions. Diabetes 52:1036–1040PubMedCrossRefGoogle Scholar
  56. 56.
    Ekinci EI, Jerums G, Skene A, Crammer P, Power D, Cheong KY, Panagiotopoulos S, McNeil K, Baker ST, Fioretto P, Macisaac RJ (2013) Renal structure in normoalbuminuric and albuminuric patients with type 2 diabetes and impaired renal function. Diabetes Care 36:3620–3626PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    MacIsaac RJ, Panagiotopoulos S, McNeil KJ, Smith TJ, Tsalamandris C, Hao H, Matthews PG, Thomas MC, Power DA, Jerums G (2006) Is nonalbuminuric renal insufficiency in type 2 diabetes related to an increase in intrarenal vascular disease? Diabetes Care 29:1560–1566PubMedCrossRefGoogle Scholar
  58. 58.
    Fioretto P, Mauer M, Brocco E, Velussi M, Frigato F, Muollo B, Sambataro M, Abaterusso C, Baggio B, Crepaldi G, Nosadini R (1996) Patterns of renal injury in NIDDM patients with microalbuminuria. Diabetologia 39:1569–1576PubMedCrossRefGoogle Scholar
  59. 59.
    Romagnani P, Remuzzi G (2013) Renal progenitors in non-diabetic and diabetic nephropathies. Trends Endocrinol Metab 24:13–20PubMedCrossRefGoogle Scholar
  60. 60.
    Chawla LS, Kimmel PL (2012) Acute kidney injury and chronic kidney disease: an integrated clinical syndrome. Kidney Int 82:516–524PubMedCrossRefGoogle Scholar
  61. 61.
    Coca SG, Singanamala S, Parikh CR (2012) Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 81:442–448PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Bucaloiu ID, Kirchner HL, Norfolk ER, Hartle JE 2nd, Perkins RM (2012) Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury. Kidney Int 81:477–485PubMedCrossRefGoogle Scholar
  63. 63.
    Kline J, Rachoin JS (2013) Acute kidney injury and chronic kidney disease: it’s a two-way street. Ren Fail 35:452–455PubMedCrossRefGoogle Scholar
  64. 64.
    Niewczas MA, Gohda T, Skupien J, Smiles AM, Walker WH, Rosetti F, Cullere X, Eckfeldt JH, Doria A, Mayadas TN, Warram JH, Krolewski AS (2012) Circulating TNF receptors 1 and 2 predict ESRD in type 2 diabetes. J Am Soc Nephrol 23:507–515PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Solini A, Penno G, Bonora E, Fondelli C, Orsi E, Arosio M, Trevisan R, Vedovato M, Cignarelli M, Andreozzi F, Nicolucci A, Pugliese G, Renal Insufficiency And Cardiovascular Events (RIACE) Study Group (2012) Diverging association of reduced glomerular filtration rate and albuminuria with coronary and noncoronary events in patients with type 2 diabetes: the renal insufficiency and cardiovascular events (RIACE) Italian multicenter study. Diabetes Care 35:143–149PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Hoefield RA, Kalra PA, Baker PG, Sousa I, Diggle PJ, Gibson MJ, O’Donoghue DJ, Middleton RJ, New JP (2011) The use of eGFR and ACR to predict decline in renal function in people with diabetes. Nephrol Dial Transplant 26:887–892PubMedCrossRefGoogle Scholar
  67. 67.
    Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:1–150CrossRefGoogle Scholar
  68. 68.
    Evans M, Bain SC, Hogan S, Bilous RW, Collaborative Study Group participants (2012) Irbesartan delays progression of nephropathy as measured by estimated glomerular filtration rate: post hoc analysis of the Irbesartan Diabetic Nephropathy Trial. Nephrol Dial Transplant 27:2255–2263PubMedCrossRefGoogle Scholar
  69. 69.
    Abuelo JG (2007) Normotensive ischemic acute renal failure. N Engl J Med 357:797–805PubMedCrossRefGoogle Scholar
  70. 70.
    Jerums G, Panagiotopoulos S, Premaratne E, Power DA, MacIsaac RJ (2008) Lowering of proteinuria in response to antihypertensive therapy predicts improved renal function in late but not in early diabetic nephropathy: a pooled analysis. Am J Nephrol 28:614–627PubMedCrossRefGoogle Scholar
  71. 71.
    de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM (2004) Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int 65:2309–2320PubMedCrossRefGoogle Scholar
  72. 72.
    Levey AS, Cattran D, Friedman A, Miller WG, Sedor J, Tuttle K, Kasiske B, Hostetter T (2009) Proteinuria as a surrogate outcome in CKD: report of a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration. Am J Kidney Dis 54:205–226PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2014

Authors and Affiliations

  1. 1.Department of Clinical and Molecular Medicine“La Sapienza” University of RomeRomeItaly

Personalised recommendations